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  1. Article ; Online: Using human iPSC-derived kidney organoids to decipher SARS-CoV-2 pathology on single cell level

    Katharina C. Reimer / Jitske Jansen / Gijs J. Overheul / Pascal Miesen / Ronald P. van Rij / Sergio H. Triana / Bart Smeets / Rebekka K. Schneider / Rafael Kramann

    STAR Protocols, Vol 3, Iss 3, Pp 101612- (2022)

    2022  

    Abstract: Summary: We describe a protocol for single-cell RNA sequencing of SARS-CoV-2-infected human induced pluripotent stem cell (iPSC)-derived kidney organoids. After inoculation of kidney organoids with virus, we use mechanical and enzymatic disruption to ... ...

    Abstract Summary: We describe a protocol for single-cell RNA sequencing of SARS-CoV-2-infected human induced pluripotent stem cell (iPSC)-derived kidney organoids. After inoculation of kidney organoids with virus, we use mechanical and enzymatic disruption to obtain single cell suspensions. Next, we process the organoid-derived cells into sequencing-ready SARS-CoV-2-targeted libraries. Subsequent sequencing analysis reveals changes in kidney cells after virus infection. The protocol was designed for kidney organoids cultured in a 6-well transwell format but can be adapted to organoids with different organ backgrounds.For complete details on the use and execution of this protocol, please refer to Jansen et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Cell biology ; Single cell ; Microbiology ; Stem cells ; Organoids ; Science (General) ; Q1-390
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

    Verónica Miguel / Carlos Rey-Serra / Jessica Tituaña / Belén Sirera / Elena Alcalde-Estévez / J. Ignacio Herrero / Irene Ranz / Laura Fernández / Carolina Castillo / Lucía Sevilla / James Nagai / Katharina C. Reimer / Jitske Jansen / Rafael Kramann / Ivan G. Costa / Ana Castro / David Sancho / José Miguel Rodríguez González-Moro / Santiago Lamas

    Redox Biology, Vol 68, Iss , Pp 102957- (2023)

    2023  

    Abstract: Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, ... ...

    Abstract Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-β-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage.
    Keywords Fibrosis ; Metabolism ; Mitochondria ; Inflammation ; COVID-19 ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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